PMID- 35850627 OWN - NLM STAT- MEDLINE DCOM- 20220721 LR - 20220731 IS - 1471-2253 (Electronic) IS - 1471-2253 (Linking) VI - 22 IP - 1 DP - 2022 Jul 18 TI - Skin/muscle incision and retraction regulates the persistent postoperative pain in rats by the Epac1/PKC-betaII pathway. PG - 230 LID - 10.1186/s12871-022-01771-w [doi] LID - 230 AB - Persistent postoperative pain causes influence the life quality of many patients. The Epac/PKC pathway has been indicated to regulate mechanical hyperalgesia. The present study used skin/muscle incision and retraction (SMIR) to induce postoperative pain in rats and evaluated the Epac/PKC pathway in postoperative pain. Mechanical allodynia was assessed by paw withdrawal threshold before and after incision. The levels of Epac, PKC, proinflammatory cytokines, and blood-nerve barrier-related proteins were assessed using Western blotting. We found that SMIR induced the activation of the Epac/PKC pathway, mechanical allodynia, and upregulation of Glut1, VEGF, and PGP9.5 proteins in dorsal root ganglia. Under the influence of agonists of Epac/PKC, normal rats showed mechanical allodynia and increased Glut1, VEGF, and PGP9.5 proteins. After inhibition of Epac1 in rats with SMIR, mechanical allodynia was alleviated, and proinflammatory cytokines and Glut1, VEGF, and PGP9.5 proteins were decreased. Moreover, dorsal root ganglia neurons showed abnormal proliferation under the activation of the Epac/PKC pathway. Using Captopril to protect vascular endothelial cells after SMIR had a positive effect on postoperative pain. In conclusion, SMIR regulates the persistent postoperative pain in rats by the Epac/PKC pathway. CI - (c) 2022. The Author(s). FAU - Qian, Jiashu AU - Qian J AD - Department of Anesthesiology, Taizhou Central Hospital (Affiliated Hospital of Taizhou University), No. 999 Donghai Avenue, Jiaojiang Economic Development Zone, Taizhou City, 318000, Zhejiang Province, China. FAU - Lin, Xuezheng AU - Lin X AD - Department of Anesthesiology, Taizhou Central Hospital (Affiliated Hospital of Taizhou University), No. 999 Donghai Avenue, Jiaojiang Economic Development Zone, Taizhou City, 318000, Zhejiang Province, China. FAU - Zhou, Zhili AU - Zhou Z AD - Department of Anesthesiology, Taizhou Central Hospital (Affiliated Hospital of Taizhou University), No. 999 Donghai Avenue, Jiaojiang Economic Development Zone, Taizhou City, 318000, Zhejiang Province, China. Zhouzhl@tzzxyy.com. LA - eng PT - Journal Article DEP - 20220718 PL - England TA - BMC Anesthesiol JT - BMC anesthesiology JID - 100968535 RN - 0 (Cytokines) RN - 0 (Glucose Transporter Type 1) RN - 0 (Guanine Nucleotide Exchange Factors) RN - 0 (Rapgef3 protein, rat) RN - 0 (Vascular Endothelial Growth Factor A) RN - EC 2.7.11.13 (Protein Kinase C beta) SB - IM MH - Animals MH - Cytokines/metabolism MH - Endothelial Cells/metabolism MH - Ganglia, Spinal/metabolism MH - Glucose Transporter Type 1 MH - Guanine Nucleotide Exchange Factors/*metabolism MH - *Hyperalgesia/complications MH - Muscles/metabolism MH - Pain, Postoperative/etiology MH - Protein Kinase C beta/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Skin MH - *Vascular Endothelial Growth Factor A PMC - PMC9290233 OTO - NOTNLM OT - Epac1/PKC-betaII OT - Persistent postoperative pain OT - Skin/muscle incision and retraction COIS- The authors declare that they have no conflicts of interest. EDAT- 2022/07/20 06:00 MHDA- 2022/07/22 06:00 PMCR- 2022/07/18 CRDT- 2022/07/19 07:37 PHST- 2022/01/07 00:00 [received] PHST- 2022/07/11 00:00 [accepted] PHST- 2022/07/19 07:37 [entrez] PHST- 2022/07/20 06:00 [pubmed] PHST- 2022/07/22 06:00 [medline] PHST- 2022/07/18 00:00 [pmc-release] AID - 10.1186/s12871-022-01771-w [pii] AID - 1771 [pii] AID - 10.1186/s12871-022-01771-w [doi] PST - epublish SO - BMC Anesthesiol. 2022 Jul 18;22(1):230. doi: 10.1186/s12871-022-01771-w.